A Study to Evaluate the Safety and Preliminary Efficacy of a Response-guided Dose Titration of KER-047 in the Treatment of Functional IDA (Iron Deficiency Anemia).

NCT05927012 | Withdrawn Phase 2 DMC

• 1 other identifier: KER047-IR-202
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 5

Brief Summary

This study aims to explore the safety and preliminary efficacy of a response-guided dose titration of KER-047 in the treatment of functional IDA (Iron deficiency anemia) in MDS (Myelodysplastic syndrome), MF(Myelofibrosis), and MDS/MPN (Myeloproliferative neoplasm) overlap syndromes.

Conditions

Iron Deficiency Anemia

Keywords

Functional Iron Deficiency Anemia (Functional IDA); Myelodysplastic Syndromes (MDS); Myelofibrosis (MF); Myelodysplastic Syndrome (MDS); Myeloproliferative Neoplasm Overlap Syndromes (MPN)

Outcome Measures

Primary Outcomes (15)

• Percentage of participants experiencing Treatment-emergent adverse events (TEAEs)

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Dose limiting toxicities (DLTs)

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Percentage of participants experiencing Treatment-related AEs (Adverse events)

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Number of participants discontinuing due to AEs (Adverse events)

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Change from Baseline in clinical laboratory values

  To determine the safety and tolerability based on changes from baseline in select clinical laboratory parameters including: Alkaline phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, Glucose, Potassium, Sodium, Total bilirubin, Folate, WBC count, Platelet Count, Reticulocyte Count, Transferrin Saturation percentage. Note - Select safety parameters will be listed as separate outcomes during results update.

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Systolic Blood Pressure

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Diastolic Blood Pressure

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Respiratory rate

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Heart rate

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Body temperature

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Fridericia corrected QT interval via 12-lead Electrocardiogram (ECG)

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• QT interval via 12-lead Electrocardiogram (ECG)

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• QRS interval via 12-lead Electrocardiogram (ECG)

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• PR interval via 12-lead Electrocardiogram (ECG)

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Body weight (in kg)

  To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

Secondary Outcomes (13)

• Change from baseline in reticulocyte hemoglobin content (RET-He)

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Change from baseline in hepcidin concentration

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Change from baseline in hemoglobin (Hgb)

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Proportion of participants who have Hgb increase of ≥1.0 g/dL (0.6 mmol/L)

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

• Proportion of participants who have Hgb increase of ≥1.5 g/dL (0.9 mmol/L)

  Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension

Study Arms (2)

Part 1 (Initial Titration Strategy)

EXPERIMENTAL

KER-047(30 mg, 60mg or 80mg) oral tablet daily (or every other day) for up to 24 weeks.

Drug: KER-047

Part 2 (Cohort Expansion or Alternate Titration Strategy)

EXPERIMENTAL

The starting dose regimen and titration schedule of KER-047 oral tablet will be based on the SRC (Safety Review Committee) recommendation from Part 1.

Drug: KER-047

Interventions

KER-047 DRUG

Oral tablet, daily (or every other day) administration

Part 1 (Initial Titration Strategy); Part 2 (Cohort Expansion or Alternate Titration Strategy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 years of age, at the time of signing informed consent.
• One of the following:
• Diagnosis of MDS according to the 2016 World Health Organization (WHO) classification that meets Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease with bone marrow blast percentage \<5% within 6 months prior to Day 1 (D1).
• Diagnosis of primary myelofibrosis, post polycythemia vera MF, or post-essential thrombocytopenia MF according to the 2017 WHO criteria with bone marrow and peripheral blood blast percentage \<2%, or stable between 2% to 5% over 6 months.
• Diagnosis of MDS/MPN overlap syndromes according to the 2016 WHO classification, with bone marrow blast percentage \<5% within 6 months prior to D1.
• Anemia with iron-restricted erythropoiesis as assessed by laboratory criteria during screening.
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local study participant privacy regulations.
• Females of childbearing potential and sexually active males must meet the contraception requirements as outlined in the protocol.

You may not qualify if:

• Active infection within 14 days of D1.
• IPSS-R score indicating high or very high risk MDS, accelerated myelofibrosis (defined as \>10% blasts), or diagnosis of acute leukemia.
• Diagnosis of hemolytic anemia.
• Diagnosis of porphyria.
• Anemia due to blood loss 28 days prior to D1.
• Diagnosis of thalassemia, thalassemia trait, or other hemoglobinopathy.
• History of drug or alcohol abuse, as defined by the Investigator, within the past 2 years.
• History of stroke, arterial embolism, or deep venous thrombosis within 6 months prior to D1.
• Known positive for human immunodeficiency virus, active infectious hepatitis B virus or active infectious hepatitis C virus.

Sponsors & Collaborators

• Keros Therapeutics, Inc.: lead

Study Sites (5)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Hadassah University Medical Center

Jerusalem, 9112001, Israel

Location

Galilee Medical Center

Nahariya, 2633737, Israel

Location

Laniado Hospital - Sanz Medical Center

Netanya, 4244916, Israel

Location

Shamir Medical Center (Assaf Harofeh Medical Center)

Zrifin, 7033001, Israel

Location

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Myelodysplastic Syndromes; Primary Myelofibrosis

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2 parts: Part 1 Initial Titration Strategy and Part 2 Cohort Expansion or Alternate Titration Strategy

Study Record Dates

• First Submitted: June 8, 2023
• First Posted: July 3, 2023
• Study Start: November 30, 2023
• Primary Completion: August 29, 2025
• Study Completion: January 4, 2026
• Last Updated: November 24, 2023

Record last verified: 2023-11

Locations

AU (1); IL (4)